胞内信号结构优化的BCMA-E-CAR-T细胞功能与安全性

doi:10.3870/j.issn.1672-8009.2026.05.001

医学分子生物学杂志 ›› 2026, Vol. 23 ›› Issue (5): 477-484.doi: 10.3870/j.issn.1672-8009.2026.05.001

• 论著 • 下一篇

胞内信号结构优化的BCMA-E-CAR-T细胞功能与安全性

李琰龙^1#, 王鹏举^2#, 张仪婷³, 秦炜炜⁴, 杨安钢², 阎博³

¹河南医药大学医学技术学院河南省新乡市, 453003;
空军军医大学基础医学院 ²免疫学教研室, ³生物化学与分子生物学教研室西安市, 710032;
⁴空军军医大学唐都医院血液内科西安市, 710038

收稿日期:2026-05-22 出版日期:2026-09-30 发布日期:2026-09-30
通讯作者: 阎博（E-mail：yanbo5870@fmmu.edu.cn）,杨安钢（E-mail：agyan@fmmu.edu.cn）
作者简介:#:共同第一作者
基金资助:
陕西省卫生健康科研创新平台（No.2025PT-07）,陕西省重点项目-实验室重点项目（No.2025SYS-SYSZD-030）

Functions and Safety of Intracellular Structure-Optimized BCMA-E-CAR-T Cells

LI Yanlong^1#, WANG Pengju^2#, ZHANG Yiting³, QIN Weiwei⁴, YANG Angang², YAN Bo³

¹Medical Technology College, Henan Medicine University, Xinxiang, Henan, 453003, China;
²Department of Immunology, ³Department of Biochemistry and Molecular Biology, Air Force Medical University, Xi'an, 710032, China;
⁴Department of Hematology, Tangdu Hospital of Air Force Medical University, Xi'an, 710038, China

Received:2026-05-22 Online:2026-09-30 Published:2026-09-30
Contact: YAN Bo（E-mail：yanbo5870@fmmu.edu.cn）,YANG Angang（E-mail：agyan@fmmu.edu.cn）
About author:#:These authors contributed equally as first author.
Supported by:
Health Research and Innovation Platform of Shaanxi Provincial Health Commission（No.2025PT-07）, the Key Project of Shaanxi Province - Laboratory Key Project（No. 2025SYS-SYSZD-030）

摘要/Abstract

摘要： 目的构建包含不同胞内信号结构域的CAR-T细胞,以解决传统CAR-T细胞因胞内激活信号过强而导致的过早耗竭、效能不足及不可控的细胞因子风暴等核心问题。方法将CAR结构的胞内信号域CD3ζ,替换为仅含一个免疫受体酪氨酸激活基序的CD3ε信号域,构建新型BCMA-E-CAR-T细胞;应用流式细胞术检测该CAR-T细胞对靶细胞的杀伤效率、活化程度、耗竭水平、中央记忆表型分化、细胞增殖能力及细胞因子分泌水平。结果 BCMA-E-CAR-T细胞表现出显著增强的对靶细胞的细胞毒性,同时具有更低的活化程度、更低的耗竭水平、减少的细胞因子释放、增强的中央记忆表型分化以及增殖潜能。结论本研究成功构建了以CD3ε为胞内激活信号域的新型BCMA-E-CAR-T细胞,并在体外抗肿瘤模型中证实其具有增强的抗肿瘤效应与更高的治疗安全性。

关键词: 嵌合抗原受体T细胞, B细胞成熟抗原, CD3ε, 免疫受体酪氨酸激活基序, 细胞因子释放综合征, 耗竭

Abstract: Objective To construct CAR-T cells harboring distinct intracellular signaling domains, thereby addressing the core limitations of conventional CAR-T cells, including premature exhaustion, insufficient antitumor efficacy, and uncontrolled cytokine release syndrome caused by excessive intracellular activation signals. Methods The intracellular signaling domain CD3ζ of the conventional CAR construct was replaced with the CD3ε signaling domain containing only one immunoreceptor tyrosine-based activation motif （ITAM）, to generate a novel BCMA-E-CAR-T cell product. Flow cytometry was employed to assess the cytotoxicity against target cells, activation status, exhaustion profile, central memory phenotype differentiation, proliferative capacity, and cytokine secretion levels of the engineered CAR-T cells. Results BCMA-E-CAR-T cells exhibited significantly enhanced cytotoxicity against target cells, accompanied by reduced activation levels, alleviated exhaustion, diminished cytokine release, elevated differentiation toward a central memory phenotype, and stronger proliferative potential. Conclusion This study successfully constructed novel BCMA-E-CAR-T cells harboring CD3ε as the intracellular activation signaling domain, which exhibited significantly enhanced antitumor activity and improved therapeutic safety in tumor models.

Key words: CAR-T, B-cell maturation antigen, CD3ε, immune receptor tyrosine activation motif, exhaustion, cytokine release syndrome

中图分类号:

R457.2

李琰龙, 王鹏举, 张仪婷, 秦炜炜, 杨安钢, 阎博. 胞内信号结构优化的BCMA-E-CAR-T细胞功能与安全性[J]. 医学分子生物学杂志, 2026, 23(5): 477-484.

LI Yanlong, WANG Pengju, ZHANG Yiting, QIN Weiwei, YANG Angang, YAN Bo. Functions and Safety of Intracellular Structure-Optimized BCMA-E-CAR-T Cells[J]. Journal of Medical Molecular Biology, 2026, 23(5): 477-484.

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胞内信号结构优化的BCMA-E-CAR-T细胞功能与安全性

Functions and Safety of Intracellular Structure-Optimized BCMA-E-CAR-T Cells

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